Targeting ß Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats.
Autores da FMUP
Participantes de fora da FMUP
- Cristelo C
- Pinto S
- Marques JM
- Gama FM
- Sarmento B
Unidades de investigação
Abstract
Type 1 diabetes (T1D) is an incurable condition with an increasing incidence worldwide, in which the hallmark is the autoimmune destruction of pancreatic insulin-producing ß cells. Cathelicidin-based peptides have been shown to improve ß cell function and neogenesis and may thus be relevant while developing T1D therapeutics. In this work, a cathelicidin-derived peptide, LLKKK18, was loaded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), surface-functionalized with exenatide toward a GLP-1 receptor, aiming the ß cell-targeted delivery of the peptide. The NPs present a mean size of around 100 nm and showed long-term stability, narrow size distribution, and negative ?-potential (-10 mV). The LLKKK18 association efficiency and loading were 62 and 2.9%, respectively, presenting slow and sustained in vitro release under simulated physiologic fluids. Glucose-stimulated insulin release in the INS-1E cell line was observed in the presence of the peptide. In addition, NPs showed a strong association with ß cells from isolated rat islets. After administration to diabetic rats, NPs induced a significant reduction of the hyperglycemic state, an improvement in the pancreatic insulin content, and glucose tolerance. Also remarkable, a considerable increase in the ß cell mass in the pancreas was observed. Overall, this novel and versatile nanomedicine showed glucoregulatory ability and can pave the way for the development of a new generation of therapeutic approaches for T1D treatment.
© 2023 American Chemical Society.
Dados da publicação
- ISSN/ISSNe:
- 2575-9108, 2575-9108
- Tipo:
- Article
- Páginas:
- 1544-1560
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE American Chemical Society
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Citar a publicação
Cristelo C,Nunes R,Pinto S,Marques JM,Gama FM,Sarmento B. Targeting ß Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats. ACS Pharmacol Transl Sci. 2023. 6. (10):p. 1544-1560.